Xenotransplantation has the potential to provide organs for the 60,000 patients waiting for transplants, and to therefore eliminate the 4,000 deaths occur every year due to a lack of donor organs. For the safety of the general public, it is essential that the organs be supplied with a minimized microbiological burden to prevent new zoonotic infections spreading in the human population. The innovative aim of this research proposal is to develop the DID haplotype miniature swine as the donor animal of choice for xenotransplantation. These animals are unique amongst all strains of pig tested due to their absence of infectious human-tropic pig endogenous retrovirus (PERV). PERV, and other latent organisms such as herpesviruses, represent a particular microbiological safety concern for xenotransplantation. The studies proposed seek to determine the genetic basis for the lack of human-tropic PERV. Once defined, the information may facilitate the breeding of other breeds of PERV-free animals. Pig herpesviruses are another serious safety concern for xenotransplantation. Studies seek to investigate the biology of a recently discovered porcine gamma-herpesvirus. The development of technologies that enable both the control and eradication of this agent are proposed. PROPOSED COMMERCIAL APPLICATION: In excess of 60,000 people are currently waiting for organ transplants due to a lack of donor organs. Xenotransplantation has the potential to relieve this shortage. The unique absence of human-tropic PERV in the inbred D/D haplotype miniature swine make it ideal to be developed as the animal of choice to supply the tissues used for all xenotransplants.